Biao Du

Bioinspired total synthesis of bolivianine: a Diels-Alder/intramolecular hetero-Diels-Alder cascade approach.

We report the first total synthesis of bolivanine in a 14-step pathway involving the synthesis of onoseriolide. Our synthesis features a palladium-catalyzed intramolecular cyclopropanation involving an allylic metal carbene and a Diels-Alder/intramolecular hetero-Diels-Alder cascade, allowing the single-step assembly of a tricyclic system with proper configuration. The synthetic efforts validate our modified biogenetic hypothesis and allow us to confirm the absolute configuration of bolivianine.

Asymmetric Total Synthesis of Onoseriolide, Bolivianine, and Isobolivianine

In this article, we describe our efforts on the total synthesis of bolivianine (1) and isobolivianine (2), involving the synthesis of onoseriolide (3). The first generation synthesis of bolivianine was completed in 21 steps by following a chiral resolution strategy. Based on the potential biogenetic relationship between bolivianine (1), onoseriolide (3), and β-(E)-ocimene (8), the second generation synthesis of bolivianine was biomimetically achieved from commercially available (+)-verbenone in 14 steps. The improved total synthesis features an unprecedented palladium-catalyzed intramolecular cyclopropanation through an allylic metal carbene, for the construction of the ABC tricyclic system, and a Diels-Alder/intramolecular hetero-Diels-Alder (DA/IMHDA) cascade for installation of the EFG tricyclic skeleton with the correct stereochemistry. Transformation from bolivianine to isobolivianine was facilitated in the presence of acid. The biosynthetic mechanism and the excellent regio- and endo selectivities in the cascade are well supported by theoretical chemistry based on the DFT calculations.

Total Synthesis of the Lindenane-Associated Terpenoids

Abstract Lindenane-type sesquiterpenoids are characteristic metabolites in the genus Chloranthus . These natural sesquiterpenoid monomers and the associated sesquiterpenoid dimers and sesterterpenoids are intriguing because of their complex and novel molecular architecture and significant bioactivities. Herein, establishment of synthetic routes toward lindenane-associated sesquiterpenoid monomers and sesterterpenoids in this natural family is described in detail. The process of simplifying a lengthy synthesis to a concise one is showcased through illumination of new ideas and development of novel methodology. A number of total syntheses of target molecules were conceived and realized, during which unexpected experimental discoveries were made, which then served as inspiration for the development of useful synthetic methodology. Importantly, the practice of total synthesis showed that we should be inspired but not limited by biogenetic hypotheses of target molecules and that the biohypothesis could be modified and improved based on the understanding of key reactions explored in chemical synthesis.